rs397517918

Description

p.Tyr527Asn, c.1579T>A (EYA1; NM_172058.2; Chr8g.72127640A>T; GRCh37): The p.Tyr 527Asn variant in EYA1 has been reported in 2 individuals with Branchio-oto-rena l syndrome and segregated with disease in 3 affected relatives (Orten 2008, LMM data). This variant has not been reported in large population studies. A differ ent amino acid change at the same codon (p.Tyr527Cys) was identified in two prob ands with Branchio-oto-renal syndrome, suggesting that a change of amino acid at this position may not be tolerated (Orten 2008, Krup 2011). Computational predi ction tools and conservation analysis suggest that this variant may impact the p rotein, though this information is not predictive enough to determine pathogenic ity on its own. In summary, although additional studies are required to fully es tablish its clinical significance, this variant is likely pathogenic for autosom al dominant Branchio-oto-renal syndrome based on its occurrence in multiple affe cted individuals with clinical features of BOR, segregation with phenotypes in f amily members, extremely low allele frequency in the general population, and sup portive functional predictions.